Relationship of airway responsiveness with airway morphometry in normal and immunized rabbits.

Airway responses to chemical stimuli occur over a wide range of concentrations, with overlap between severe, moderate and mild asthmatic groups and with normal healthy individuals. Mathematical modelling has suggested that relative thickness of the airway wall may account for this range of responsiveness. We have investigated whether in vivo airway responsiveness varies as a function of airway wall thickness in terms of airway smooth muscle area in normal and immunized New Zealand White (NZW) rabbits. Airway responsiveness to inhaled methacholine (MCh) was determined in vivo under neuroleptanalgesia. Subsequently, ex vivo responsiveness to MCh (pD(2)=-log EC(50)) of isolated bronchi from the same animal was established. Smooth muscle area per mm basement membrane (SM/mmBM) was also measured morphometrically in the tested bronchi and the findings related to in vivo and ex vivo responsiveness. We found no relationship between airway responsiveness in vivo and pD(2)values in either immunized or control rabbits. In both control and immunized rabbits, no correlation was found between SM/mmBM and in vivo airway responsiveness. Only in immunized animals with a PCA titre >0, was there a significant correlation (=-0.5986, P<0.05) between SM/mmBM and pD(2). We conclude that airway smooth muscle area per se is not the sole contributor of airway responsiveness in vivo in normal rabbits.

Effect of antagonists for NK(2)and B(2) receptors on antigen-induced airway responses in allergic rabbits.

The effects of the tachykinin NK(2)receptor antagonist, MEN 11420 (300 nmol/kg) and the bradykinin B(2)receptor antagonist, CP 0597 (17.2 and 172 nmol/kg) were studied in a rabbit model of antigen-induced airway responses. Antigen inhalation induced acute bronchoconstriction, airway hyperresponsiveness to histamine, and pulmonary eosinophil infiltration in 3-month-old rabbits immunized with Alternaria tenuis antigen within 24 h of birth. Treatment with MEN 11420 significantly reduced the acute bronchoconstriction induced by antigen, in terms of lung resistance. Antigen-induced changes in dynamic compliance were unaffected. CP 0597 had no effect on antigen-induced changes in lung function. Neither MEN 11420 nor CP 0597 had a significant effect on the antigen-induced increase in airway responsiveness to inhaled histamine or the pulmonary eosinophil infiltration 24 h after antigen challenge. We conclude that blockade of the NK(2)receptor can alter acute airway responses to antigen, but not antigen-induced eosinophilia or hyperresponsiveness to histamine. We also conclude that bradykinin B(2)receptor-mediated responses do not play a role in airway responses to antigen.